Fatima Soghra, Zhou Sheng, Sorrentino Brian P
Division of Experimental Hematology, Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Division of Experimental Hematology, Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Exp Hematol. 2018 Sep;65:29-33. doi: 10.1016/j.exphem.2018.06.286. Epub 2018 Jun 30.
Abcg2, a member of the ATP-binding cassette transporter family, is expressed in adult hematopoietic stem cells (HSCs) and is required for the side population phenotype of adult bone marrow HSCs and other adult tissue-specific stem cells. Lineage tracing in adult mice using the Abcg2-Cre mouse model showed that Abcg2 marks HSCs, intestinal stem cells, and spermatogonial stem cells. It is unclear whether definitive HSCs or their precursors in early embryonic development can be marked by Abcg2 expression. Here, we treated pregnant Abcg2 Cre/Cre RosaLSL-YFP mice with a single injection of 4-hydroxytamoxifen at embryonic day 7.5. Four months after birth, a small yellow fluorescent protein-positive (YFP) cell population could be detected in all of the major white blood cell lineages and this was stable for 8 months. Transplant of bone marrow cells or Sca1YFP cells from these mice showed continued multilineage marking in recipient mice at 4 months. These results demonstrate that Abcg2 expression marks precursors to adult long-term repopulating HSCs at E7.5 to E8.5 and contributes to a stable subpopulation of HSCs well into adulthood.
Abcg2是ATP结合盒转运蛋白家族的成员之一，在成体造血干细胞（HSC）中表达，是成体骨髓HSC和其他成体组织特异性干细胞侧群表型所必需的。使用Abcg2-Cre小鼠模型对成年小鼠进行谱系追踪表明，Abcg2标记HSC、肠道干细胞和精原干细胞。目前尚不清楚在早期胚胎发育中，确定的HSC或其前体细胞是否可以通过Abcg2表达进行标记。在此，我们在胚胎第7.5天对怀孕的Abcg2 Cre/Cre RosaLSL-YFP小鼠单次注射4-羟基他莫昔芬。出生四个月后，在所有主要白细胞谱系中均可检测到一小群黄色荧光蛋白阳性（YFP）细胞，且这种情况持续了8个月。移植这些小鼠的骨髓细胞或Sca1YFP细胞后，受体小鼠在4个月时仍持续出现多谱系标记。这些结果表明，Abcg2表达在胚胎第7.5天至第8.5天标记了成年长期重建HSC的前体细胞，并有助于形成一个稳定的HSC亚群，直至成年期。
